Multiple Phase 1/2 Cohorts of Nivolumab Monotherapy or Nivolumab Combination Regimens Across Relapsed/Refractory Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 320
- 试验地点
- 41
- 主要终点
- Number of Participants That Experienced Drug Related Grade 3-4 AEs
研究概览
简要总结
The purpose of this study is to determine the side effects of treatment of the combination of nivolumab and daratumumab in participants with relapsed/refractory multiple myeloma.
详细描述
NOTE: Currently, this study is only open to nivolumab+daratumumab vs daratumumab monotherapy in multiple myeloma patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have received at least 3 prior lines of therapy, including a proteasome inhibitor [PI] and an immunomodulatory agent [IMiD] OR have disease that is double refractory to a PI and IMiD
- •More than 12 weeks post-transplant of your own blood forming stem cells (autologous transplant)
- •Have detectable disease measured by a specific protein in your blood and/or urine
- •Must consent to bone marrow aspirate or biopsy.
排除标准
- •Solitary bone or extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia, or monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), primary amyloidosis, Waldenstrom's macroglobulinemia, POEMS syndrome or active plasma cell leukemia
- •Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti CTLA 4, or anti-CD38 antibody, or allogeneic stem cell transplantation
- •Seropositive for human immunodeficiency virus (HIV), Hepatitis B surface antigen or Hepatitis C antibody positive (except if HCV-RNA negative), or history of active chronic hepatitis B or C
- •History of central nervous system involvement or symptoms suggestive of central nervous system involvement by multiple myeloma
- •Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
Nivolumab monotherapy (Dose Escalation)
Nivolumab solution intravenously as specified
Non-randomized
Enrollment is closed for this cohort
干预措施: Nivolumab (Biological)
Nivolumab + Ipilimumab
Nivolumab and Ipilimumab solution intravenously as specified
Non-randomized
Enrollment is closed for this cohort
干预措施: Nivolumab (Biological)
Nivolumab + Ipilimumab
Nivolumab and Ipilimumab solution intravenously as specified
Non-randomized
Enrollment is closed for this cohort
干预措施: Ipilimumab (Biological)
Nivolumab + Lirilumab
Non-randomized
Nivolumab: 3 mg/kg given every 2 weeks Lirilumab: 3 mg/kg given every 4 weeks
Enrollment is closed for this cohort
干预措施: Nivolumab (Biological)
Nivolumab + Lirilumab
Non-randomized
Nivolumab: 3 mg/kg given every 2 weeks Lirilumab: 3 mg/kg given every 4 weeks
Enrollment is closed for this cohort
干预措施: Lirilumab (Biological)
Nivo + Dara + Pom + Dexa vs. Nivo + Dara
Randomized
Nivolumab:
Cycle 1: 240 mg Day 15 Cycle 2-6: 240 mg Days 1, 15 Cycle 7 & beyond: 480 mg Day 1
Daratumumab:
Cycle 1-2: 16 mg/kg Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg Days 1, 15 Cycle 7 & beyond: 16 mg/kg Day 1
Pomalidomide:
4 mg po (by mouth) daily on Days 1 - 21 of each 28-day cycle
Dexamethasone:
Weeks without daratumumab dosing:
- 40 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants ≤ 75 years old
- 20 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants > 75 years old
Weeks with daratumumab dosing:
- 20 mg iv before the daratumumab infusion and 20 mg po after the daratumumab infusion in participants ≤ 75 years old
- 16 mg iv before the daratumumab infusion and 4 mg po after the daratumumab infusion in participants > 75 years old
Enrollment is closed for this cohort
干预措施: Nivolumab (Biological)
Nivo + Dara + Pom + Dexa vs. Nivo + Dara
Randomized
Nivolumab:
Cycle 1: 240 mg Day 15 Cycle 2-6: 240 mg Days 1, 15 Cycle 7 & beyond: 480 mg Day 1
Daratumumab:
Cycle 1-2: 16 mg/kg Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg Days 1, 15 Cycle 7 & beyond: 16 mg/kg Day 1
Pomalidomide:
4 mg po (by mouth) daily on Days 1 - 21 of each 28-day cycle
Dexamethasone:
Weeks without daratumumab dosing:
- 40 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants ≤ 75 years old
- 20 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants > 75 years old
Weeks with daratumumab dosing:
- 20 mg iv before the daratumumab infusion and 20 mg po after the daratumumab infusion in participants ≤ 75 years old
- 16 mg iv before the daratumumab infusion and 4 mg po after the daratumumab infusion in participants > 75 years old
Enrollment is closed for this cohort
干预措施: Daratumumab (Biological)
Nivo + Dara + Pom + Dexa vs. Nivo + Dara
Randomized
Nivolumab:
Cycle 1: 240 mg Day 15 Cycle 2-6: 240 mg Days 1, 15 Cycle 7 & beyond: 480 mg Day 1
Daratumumab:
Cycle 1-2: 16 mg/kg Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg Days 1, 15 Cycle 7 & beyond: 16 mg/kg Day 1
Pomalidomide:
4 mg po (by mouth) daily on Days 1 - 21 of each 28-day cycle
Dexamethasone:
Weeks without daratumumab dosing:
- 40 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants ≤ 75 years old
- 20 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants > 75 years old
Weeks with daratumumab dosing:
- 20 mg iv before the daratumumab infusion and 20 mg po after the daratumumab infusion in participants ≤ 75 years old
- 16 mg iv before the daratumumab infusion and 4 mg po after the daratumumab infusion in participants > 75 years old
Enrollment is closed for this cohort
干预措施: Pomalidomide (Drug)
Nivo + Dara + Pom + Dexa vs. Nivo + Dara
Randomized
Nivolumab:
Cycle 1: 240 mg Day 15 Cycle 2-6: 240 mg Days 1, 15 Cycle 7 & beyond: 480 mg Day 1
Daratumumab:
Cycle 1-2: 16 mg/kg Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg Days 1, 15 Cycle 7 & beyond: 16 mg/kg Day 1
Pomalidomide:
4 mg po (by mouth) daily on Days 1 - 21 of each 28-day cycle
Dexamethasone:
Weeks without daratumumab dosing:
- 40 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants ≤ 75 years old
- 20 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants > 75 years old
Weeks with daratumumab dosing:
- 20 mg iv before the daratumumab infusion and 20 mg po after the daratumumab infusion in participants ≤ 75 years old
- 16 mg iv before the daratumumab infusion and 4 mg po after the daratumumab infusion in participants > 75 years old
Enrollment is closed for this cohort
干预措施: Dexamethasone (Drug)
Daratumumab vs. Nivolumab + Daratumumab
Randomized
Nivolumab:
Cycle 1: 240 mg Day 15 Cycle 2 & beyond: 480 mg Day 1
Daratumumab:
Cycle 1-2: 16 mg/kg Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg Days 1, 15 Cycle 7 & beyond: 16 mg/kg Day 1
干预措施: Nivolumab (Biological)
Daratumumab vs. Nivolumab + Daratumumab
Randomized
Nivolumab:
Cycle 1: 240 mg Day 15 Cycle 2 & beyond: 480 mg Day 1
Daratumumab:
Cycle 1-2: 16 mg/kg Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg Days 1, 15 Cycle 7 & beyond: 16 mg/kg Day 1
干预措施: Daratumumab (Biological)
结局指标
主要结局
Number of Participants That Experienced Drug Related Grade 3-4 AEs
时间窗: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
Number and percent of participants that experienced drug related Grade 3-4 AEs occurring up to 100 days after the last dose of study drug.
Number of Participants That Experienced Drug Related Grade 3-4 SAEs
时间窗: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
Number and percent of participants that experienced drug related Grade 3-4 SAEs occurring up to 100 days after the last dose of study drug.
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Liver
时间窗: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
Number and percent of participants that experienced drug related Grade 3-4 AEs occurring up to 100 days after the last dose of study drug.
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Thyroid
时间窗: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
Number of Participants That Experienced Drug-related Grade 3-4 AEs in the Nivolumab + Daratumumab Cohort
时间窗: approximately up to 4 years
Number of Participants That Experienced Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort
时间窗: approximately up to 4 years
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Hematology
时间窗: approximately up to 4 years
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Liver
时间窗: approximately up to 4 years
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Thyroid
时间窗: approximately up to 4 years
次要结局
- Best Overall Response(Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month)
- Progression Free Survival Rate(From randomization to the specified timepoints (up to 48 months))
- Progression Free Survival in the Nivolumab + Daratumumab Cohort(approximately up to 4 years)
- Tmax in the Nivolumab + Daratumumab Cohort(approximately up to 4 years)
- Best Overall Response - Multiple Myeloma Group(Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month)
- AUC (0-T) in the Nivolumab + Daratumumab Cohort(approximately up to 4 years)
- AUC (TAU) in the Nivolumab + Daratumumab Cohort(approximately up to 4 years)
- Duration of Response(Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to approximately 37 months Nivo Liri: approximately up to 4 years 1 month)
- Duration of Response - Multiple Myeloma Group(Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month)
- Overall Survival(Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to3 years Nivo Liri: approximately up to 4 years 1 month)
- Number of Participants With PD-L1 Expression(At baseline (prior to start of study treatment))
- Duration of Response in the Nivolumab + Daratumumab Cohort(approximately up to 4 years)
- Cmax in the Nivolumab + Daratumumab Cohort(approximately up to 4 years)
- End of Infusion Nivolumab Concentration Levels in the Nivolumab + Daratumumab Cohort(Measurements collected at cycles 1, 2, 3, 5, 7, and 11; each cycle is 28 days)
- Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort(approximately up to 4 years)
- Objective Response Rate in the Nivolumab + Daratumumab Cohort(approximately up to 4 years)
- Cmin in the Nivolumab + Daratumumab Cohort(approximately up to 4 years)
- Progression Free Survival(From date of randomization to date of progression or death, whichever occurs first (up to approximately 24 months))
- Percentage Change From Baseline in the Modified Severity Weighted Assessment Tool (mSWAT) Score(From baseline (last measurement before start of study treatment) to last available measurement after start of study treatment (88 weeks for Nivo mono, 93 weeks for nivo+ipi, 25 weeks for nivo+liri))